In the organic synthesis of a compound having a functional group such as a hydroxyl group, an amino group and the like, appropriate protection of the functional group is important for synthesis tactics.
Acetal type protecting group represented by the formula (II): —CH2OR (II) wherein R is a phenyl group optionally having substituent(s), an alkyl group optionally having substituent(s) or a benzyl group optionally having substituent(s), which is exemplified by a methoxymethyl group, an ethoxymethyl group, a methoxyethoxymethyl group and the like, hereinafter to be also referred to as protecting group (II), is used as a hydroxyl-protecting group. Since the group is stable under various reaction conditions and can be easily deprotected under weak acidic conditions, it is highly valuable for use as a hydroxyl-protecting group.
As a method of protecting a hydroxyl group with protecting group (II), 1) a method comprising reaction by adding dropwise alkoxymethyl chloride in the presence of a small excess of diisopropylethylamine and 2) a method comprising reacting a large excess of dialkoxymethane with heating in the presence of a strong acid catalyst are known (Protective Groups in organic Synthesis, 3rd Edition, Wiley Interscience Publication, John Wiley & Sons, Inc., 1999, p. 27-49).
However, the reaction system of 1) is associated with problems in that it requires basic conditions and cannot be employed for the protection of alcohol unstable to base, and that highly toxic alkoxymethyl chloride is used. The reaction system of 2) is associated with problems in that it requires strong acidic conditions and cannot be employed for the protection of alcohol unstable to acid, that it is uneconomical due to the use of a large excess of dialkoxymethane, and further that the reaction tends to be complicated because it involves equilibrium reaction and the like.
In view of the above, a method capable of introducing protecting group (II) under mild conditions into general alcohols including alcohol unstable to acid or base has been desired.